Iontophoresis is a safe, well-documented method applying drugs which are charged; application of an electrical current assists penetration of the drug into surface tissues. We have found that 9-beta-D-arabinofuranosyladenine-5'-phosphate (Ara-AMP) and idoxuridine (IDU) administered by iontophoresis into neonatal and adult mouse skin and into rabbit eyes have a greatly increased rate of penetration when compared with topical application. Ara-AMP, a new anti-viral agent, is ideally suited for iontophoresis because it is highly charged in aqueous solution. Furthermore, animal studies by others indicate the Ara-AMP has a high degree of anti-viral activity with less toxicity than IDU, phosphonoacetic acid, or Ara C. We will evaluate the chemotherapeutic efficacy of Ara-AMP, IDU, and Ara-A by topical and iontophoretic application to lesions in three animal models: a) the skin of hairless mice infected with Herpes simplex virus (HSV) type 1 and 2, b) the rabbit eye infected with HSV type 1, and c) the guinea pig vagina infected with HSV type 2. These three models mimic the human infections of herpes labialis, herpes keratitis, and herpes genitalis. HSV infections in these animal models will be studied for control of the surface lesion and prevention of spread of the disease. Furthermore, long term studies (over a six month to 1 year period) will include analysis of liver, kidney, brain, cornea, retina, and skin epithelium for evidence of HSV lesions or possible genetic damage and carcinogenesis. These studies can establish whether iontophoresis of Ara-AMP in animal models is: a) safe and effective, b) superior to topical application of Ara-AMP, Ara-A, and IDU, and c) superior to iontophoresis of IDU. If the assurance is obtained that iontophoretically assisted delivery of Ara-AMP is successful in the treatment of HSV infections, it will offer the promise that this procedure will become useful in the application of drugs to HSV infected surface tissues in humans. The successful application of antiviral drugs by iontophoresis would have broad implications for delivery of other drugs by this method.